Biomedical subjects

Sharon L Hale

Publications and source records attributed to Sharon L Hale.

5 recordsLinked to original sources

PubMed2003

Transplantation of neonatal cardiomyocytes after permanent coronary artery occlusion increases regional blood flow of infarcted myocardium.

BACKGROUND: Cellular cardiomyoplasty is a promising approach for rebuilding scar tissue after acute myocardial infarction. However, the angiogenic potential of transplanted immature cardiomyocytes and their effect on regional myocardial blood flow (RMBF) after coronary artery occlusion remain to be evaluated. METHODS AND RESULTS: Intramyocardial injection of cultured neonatal cardiomyocytes (4 x 10(6) cells/50-70 microliter) into the scar 1 week after permanent coronary occlusion in rats resulted in improved RMBF in the infarct 4 weeks after transplantation (radioactive microspheres, 0.97 +/- 0.18 ml/min/g) in comparison to medium-injected hearts (0.61 +/- 0.11 ml/min/g, P < 0.047). The macroscopic perfusion defect after in vivo staining with the blue dye 50% Uniperse blue was significantly smaller in the cell transplantation group (1.5 +/- 0.3% of the heart) compared to the medium group (3.0 +/- 0.6%, P < 0.017). Clusters of engrafted cells within the scar demonstrated a high capillary density (1217 +/- 114 perfused (blue) capillaries/mm(2)); however, in the scar tissue itself capillary density in the cell group (156 +/- 62/mm(2)) did not significantly differ from the medium group (125 +/- 10/mm(2)), suggesting that neo-angiogenesis was confined to regions of successful engraftment (non-infarcted tissue: 1924 +/- 114 perfused capillaries/mm(2)). The transplantation group was characterized by smaller diastolic and systolic left ventricular volumes, as assessed by intravenous ventriculography, along with thickened infarcts (0.93 +/- 0.07 vs. 0.75 +/- 0.04 mm, P < 0.020) and lower infarct expansion indices (0.64 +/- 0.07 vs. 0.83 +/- 0.06, P < 0.023), as determined by post-mortem morphometry of histologic slides. CONCLUSIONS: Transplantation of neonatal cardiomyocytes induced neo-angiogenesis in zones of successful cell engraftment within the scar, which effectively enhanced tissue perfusion.

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PubMed2003

Long-term outcome of fetal cell transplantation on postinfarction ventricular remodeling and function.

OBJECTIVES: The purpose of this study was to determine the long-term outcome of fetal cell transplantation into myocardial infarction on left ventricular (LV) function and remodeling. BACKGROUND: While neonatal cell transplantation improved function for acute myocardial infarction, long-term data on the effects of cell-transplant therapy using a more primitive cell on ventricular remodeling and function are needed.Methods. - Therefore, we injected 4 x 10(6) Fischer 344 fetal cardiac cells or medium into 1-week old infarcts in adult female Fischer rats to assess long-term outcome. RESULTS: Ten months after transplantation histologic analysis showed that cell implants were readily visible within the infarct scar. Infarct wall thickness was greater in cell-treated at 0.69 +/- 0.05 mm (n = 11) vs. medium-treated hearts at 0.33 +/- 0.01 mm (n = 19; P = 0.0001). Postmortem LV volume was 0.41 +/- 0.04 ml in cell-treated vs. 0.51 +/- 0.03 ml in medium-treated hearts (P < 0.04). Ejection fraction assessed by LV angiography was 0.40 +/- 0.02 in cell-treated (n = 16) vs. 0.33 +/- 0.02 in medium-treated hearts (n = 24; P < 0.03) with trends towards smaller in vivo end-diastolic and end-systolic volumes in cell-treated vs. medium-treated hearts. Polymerase chain reaction analysis of the Sry gene of the Y chromosome was positive in four of five cell-treated and zero of five medium-treated hearts confirming viability of male cells in female donors. CONCLUSION: Over the course of 10 months, fetal cardiac cell transplantation into infarcted hearts increased infarct wall thickness, reduced LV dilatation, and improved LV ejection fraction. Thus, fetal cell-transplant therapy mitigated the longer-term adverse effects of LV remodeling following a myocardial infarction.

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PubMed2002

Elevated body temperature during myocardial ischemia/reperfusion exacerbates necrosis and worsens no-reflow.

PURPOSE: The effects of an elevated body temperature on infarct size were tested in a rabbit model of ischemia/reperfusion. METHODS: Before coronary artery occlusion, body temperature was raised from baseline at 38.6 +/- 0.1 degrees C to 40.3 +/- 0.2 degrees C in nine treated rabbits. Temperature in eight normothermic rabbits was 38.4 +/- 0.2 degrees C. Both groups received 30 min coronary occlusion and 3 h reperfusion. RESULTS: In normothermic rabbits, 36 +/- 6% of the ischemic risk region became necrotic but in hyperthermic rabbits myocardial necrosis was significantly increased to 57 +/- 3% of the risk region (P < 0.005) despite similar risk regions and an equal degree of regional myocardial blood flow (RMBF) reduction during ischemia in both groups. Infarct size correlated positively with body temperature (r = 0.66, P < 0.004). RMBF was 43% lower during reperfusion in the previously ischemic areas of hyperthermic hearts compared with the control group (P < 0.04), suggesting worsened no-reflow. CONCLUSION: Elevation in body temperature by even a few degrees can aggravate necrosis during acute myocardial infarction and worsens no-reflow.

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PubMed2002

Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusion.

No reflow after acute myocardial infarction is an important predictor of infarct size and clinical outcome. However, the exact relationship between no reflow and infarct size remains to be determined, particularly because no reflow may progress during the time course of reperfusion. Control groups of five previous protocols using the anesthetized, open-chest rabbit model of coronary artery occlusion and reperfusion were retrospectively analyzed with respect to the correlation between regional myocardial blood flow (RMBF; radioactive microspheres) and infarct size (triphenyltetrazolium chloride) in the course of reperfusion. After 30 min of occlusion, reflow (defined as the ratio of RMBF in the risk area divided by the nonischemic area) declined from hyperemic values after 30 min of reperfusion (reflow ratio: 1.33 +/- 0.81; RMBF in the risk area at the same time point: 2.25 +/- 1.04 ml x g(-1) x min(-1)) to 0.47 +/- 0.22 after 120 min and 0.46 +/- 0.13 after 180 min of reperfusion. After 120 min of ischemia, reflow at 30 min of reperfusion was 0.49 +/- 0.24 and deteriorated by 120 min of reperfusion (0.26 +/- 0.15). In every group, there was a strong correlation between infarct size and reflow (correlation coefficients: -0.62 to -0.82). The lines of regression for the groups with assessment of RMBF after 120 or 180 min of reperfusion were nearly identical regardless of the duration of ischemia. Thus microvascular reperfusion injury led to a striking decrease in RMBF within the first 2 h of reperfusion, with infarct size as the major determinant of reflow at a given time point of reperfusion.

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PubMedDate not supplied

Gene activity changes in ischemically preconditioned rabbit heart gene: discovery array study.

This study tested the hypothesis that classic ischemic preconditioning can cause changes in gene expression patterns in the rabbit heart, assessed by gene array technology. Open-chest rabbits were randomly assigned to sham-operated and ischemically preconditioned groups. The sham-operated group received 5 hours and 20 minutes of no intervention, while the ischemically preconditioned group was subjected to two episodes of preconditioning ischemia (5 minutes each) separated by 5 minutes of reperfusion, followed by an additional 5 hours and 5 minutes of reperfusion. (33)P-labeled cDNA from the sham-operated hearts and the nonischemic and preconditioned areas of the ischemically preconditioned group was hybridized to filters spotted with 18,376 human cDNA clones. Altogether, 35 genes with significantly altered expression patterns were discovered. In the preconditioned area, genes for MAPKAP kinase 3 and cathepsin G were up-regulated. In the nonischemic area, genes for GTP exchange factor, Na(+), K(+)-ATPase, Zn finger protein 35, a representative of the CEA family, cytochrome c oxidase, mitogen-responsive phosphoprotein, and Ran-binding protein were up-regulated. None of the identified genes had been previously reported to be involved in ischemic preconditioning.

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